The promise of using immunotherapeutics to treat cancer is vast. So is the amount of money and resources big pharmaceutical companies are pouring into clinical studies to determine which agents and combinations of therapies are the most effective at turning the body’s immune system into a cancer-fighting weapon.
The results so far have been mixed. Monoclonal antibodies have been shown to inhibit immune system checkpoints, the mechanisms that prevent the immune system from running amok, but these effects are not universal. While checkpoint inhibitors are effective at treating many tumor types, such as melanoma, non-small-cell lung cancer and renal cell carcinoma, they typically only work on about 20 percent of patients and can have treatment-limiting side effects.
Immunotherapy works by manipulating the cancer-immunity cycle to encourage T cells activated in the lymph nodes to attack tumor tissue – many “takes the brakes off” checkpoints so T cells can engage with specific types of cancer tissue.
To increase responsiveness, researchers are also testing numerous combinations of immunotherapy agents, both in sequence and simultaneously. The goal is to find the silver bullet for cancer: A treatment with broad coverage that not only kills tumor cells, but achieves durable benefit and long-term survival, without complications.
If immunotherapy is truly to become the silver bullet, however, it still may require a combination of therapies to hit the target. Instead of relying solely on a systemic response to immunologic agents, some researchers are testing minimally invasive therapies that may help enhance the immune response against tumors. Combining immune checkpoint inhibitors with other treatments that trigger an immune response, such as cryoblation, chemoemblisation and radioembolisation is showing strong potential for enhancing the effectiveness of immunological agents without a proportional increase in side effects.
Promising early studies conducted at research institutions around the globe (including National Cancer Institute National Institutes of Health US, Lausanne University Hospital CHUV Switzerland, National Cancer Centre Singapore) suggest attacking tumor cells with radioactive microspheres or freezing them with cryoblation probes can trigger the immune response by causing the tumors to unleash specific antigens. Another way to describe this phenomenon is that loco-regional therapies could switch so-called “cold tumors,” where the immune system doesn’t recognize or engage with the cancerous cells, into more responsive “hot” tumors, leading to therapies that improve the patient’s chances of survival.
Our long experience with these and other loco-regional therapies has taught us they are well understood by practitioners and can significantly improve patient care without adding the same level of risk as in trials of some systemic drugs. Interventional Radiologists using image-guided, minimally invasive techniques have the potential to control and optimize conditions that encourage immunogenic cell death and harvest tissue biopsies to better inform treatment.
A recent review paper from Northwestern summarized research conducted in this arena to date, showing interventional oncology procedures can trigger an immune response, and pointing to synergies when combining with checkpoint inhibition (Hickey et al., J Vasc Interv Radiol. 2017, 28(11):1487-1494)
The sheer complexity of manipulating the immune system to fight tumors demands a multidisciplinary approach combining Oncologists, Immunologists and Interventional Radiologists. To help foster this collaboration, BTG has partnered with the Society of Interventional Oncology to fund a number of studies on how immunological and loco-regional therapies interact. By helping physicians better understand how immuno-oncology agents work, we can help expand the number of cancer patients who ultimately benefit from this revolution.
Immunotherapy may indeed prove to be the silver bullet for cancer, by enlisting the patient’s own immune system to attack dangerous tumors. But even silver bullets need to be guided to the target which is the specialty of the interventional radiologist (IR). The tools IRs use to treat cancer every day may find new uses as the enabling technology for immunotherapy.
Karen Skinner is Vice President of Immuno-Oncology R&D at BTG, the global healthcare company focused on interventional medicine.